Microvesicle Formulations and Contact Allergy - Experimental Studies in In-Vitro, Mice and Man

Jakob Torp Madsen

Research output: ThesisPh.D. thesis

104 Downloads (Pure)

Abstract

Attempts to improve formulation of topical products are a continuing process i.e. to increase cosmetic
performance, enhance effects and protect ingredients from degradation. The development of micro and
nano-vesicular systems has lead to marketing of topical drugs and cosmetics using these technologies.
Several papers have reported improved clinical efficacy by encapsulating pharmaceuticals in vesicular
systems. Some vesicular systems may improve transdermal delivery of compounds compared to
conventional vehicles. Few case reports have suggested that microvesicle formulations may affect
allergenicity of topical products.
The aim of this thesis is to investigate the effect on the sensitizing and elicitation capacity of chemical
allergens encapsulated in vesicular systems.
The first part examined how the encapsulation of isoeugenol, dinitro-chloro-benzene, and potassium
dichromate in liposomes, ethosomes and polycaprolactone affects the sensitizing properties using the
OECD and FDA approved skin sensitisation test method in mice: the Local Lymph Node Assay.
Ethanolic liposome (Ethosome) formulation of lipophilic allergens increased the sensitising capacity
and polycaprolactone protected against sensitisation compared to conventional vehicles. The
formulation of the hydrophilic allergen, potassium dichromate, in all three drug delivery systems did
not affect the sensitisation capacity. Further, the effect of vesicle size was studied and conflicting
results were found.
The second part examined whether encapsulation of allergens in ethosomes affects the patch test
reactivity and outcome of the Repeated Open Application Test (ROAT) compared to test with
ethanol:water formulations. Pre-sensitized volunteer individuals were patch tested with a dilution
series of isoeugenol and methyldibromoglutaronitrile formulated in ethosomes and ethanol:water. Both
contact allergens encapsulated in ethosomes showed significantly enhanced patch test reactions
compared to the allergen preparation in ethanol:water without ethosomes. No significant difference in
the median lag time was recorded between preparations in the repeated open application test.
The third part examined the percutaneous absorption in vitro of dinitro-chloro-benzene and
isoeugenol formulated in ethosomes and ethanol:water using Franz cells and human cadaver skin. We
found no significant relationship between percutaneous skin absorption /penetration of the allergens
and the sensitising properties of the test formulations.

Conclusion
Encapsulation of lipophilic contact allergens in lipid vesicles and nanospheres may affect the
sensitising and elicitation capacity of the encapsulated allergen. Encapsulation of the hydrophilic
allergen potassium dichromate did not alter the sensitizing capacity in the Local Lymph Node Assay.
We did not find a correlation between the percutaneous skin absorption/penetration pattern and the
sensitising capacity. The clinical implications of these results are so far uncertain. However, the
cosmetic industry should consider the effect of encapsulation on a case by case basis because certain
ingredients may become more allergenic when encapsulated. Dermatologists investigating patients
with allergic reactions to consumer products using encapsulation technology should consider the risk
of false negative results, if testing with ingredients in conventional patch test vehicles. Testing with
encapsulated ingredients should be performed when possible.
Original languageEnglish
Supervisors/Advisors
  • Andersen, Klaus Ejner, Principal supervisor
  • Vogel, Stefan, Principal supervisor
  • Johansen, Jeanne Duus, Supervisor, External person
Publisher
Publication statusPublished - 2011

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